Objective
In CARDIOREPAIR, we aim to identify and repair disease-causing variants in dilated cardiomyopathy (DCM), the major contributor to heart failure. We focus on the gene RBM20 mutated in patients with a highly penetrant and aggressive form of familial DCM. We will create a comprehensive map of all possible RBM20 variants that can cause DCM and develop a therapeutic approach for mutations with the strongest effect size. Enabled by a multitude of new technologies developed in our groups, the primary goal is to characterize the complete spectrum of amino acid mutations in RBM20 by high-throughput saturation mutagenesis screens. Combined with functional readouts and multi-omics analysis of downstream processes, we will classify and score the pathogenicity of each individual mutant (objective 1). To this end, we will cover both the known DCM-causing RBM20 variants, as well as those that have not been identified in patients yet. Each mutant, represented by a typical transcriptomic, proteomic, phosphoproteomic, and microscopic fingerprint, will guide us in finding novel class-specific therapeutic strategies to revert the deviant phenotype back to the healthy state. For a subset of mutants representing each identified mutation class, we will generate mouse models and investigate changes in heart physiology and ultrastructure linked to the altered ‘ome’ profile. Our second goal is to establish a class-specific therapeutic approach for the treatment of patients harboring RBM20 mutations (objective 2). We will implement our advances in muscle-specific gene editing, focusing on prime editing and nanobody-guided approaches to specifically tackle the mutations leading to RBM20 translocation. This proposal serves as a blueprint for going from variant identification to therapy in an accelerated fashion by harnessing and combining the power of high-throughput functional genomics and bioengineering and therefore is widely applicable to other cardiovascular diseases (CVD).
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine physiology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.3.1 - The European Innovation Council (EIC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-EIC - HORIZON EIC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-EIC-2022-PATHFINDERCHALLENGES-01
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
69117 Heidelberg
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.